Recurrent herpes simplex infections are very common, and often quite severe in the immunocompromised host. The immunologic parameters involved in recovery from a primary venereal HSV infection, development of latency, reactivation of vaginal herpes infection, and possible development of cervical carcinoma, remain an enigma. The efforts of the first two years of this research project have been focussed on establishing the overall immunologic status of mice surviving a primary vaginal infection with HSV-2, the comparison of this infection with systemic intravenous infection, and the possible antiviral effects of selected immunomodulators upon the disease in immunocompromised hosts. We have shown that mice depleted of thymus-derived lymphocytes or macrophages are still protected from systemic HSV-2 infection by treatment with an immunomodulator such as pyran. These data suggest that immunotherapeutic modalities may be of benefit to patients with genetic immunodeficiencies. However, the modes of action of immunomodulators are still uncertain, and need to be delineated before a rationale for immunotherapeutic treatment can be developed. BIBLIOGRAPHIC REFERENCES: McCord, R.S. and P.S. Morahan. Pyran-induced resistance to herpes simplex type 2 in immunosuppressed mice. Abst. Ann. Mtng. A.S.M. - 1975, p.257 (abstract). Morahan, P.S., and R.S. McCord. Resistance to herpes simplex type 2 virus induced by an immunopotentiator (pyran) in immunosuppressed mice. J. Immunol. 115:311-313 (1975).